DEPO-PROVERA 150MG/ML VIAL

Active substance: MEDROXYPROGESTERONE ACETATE

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Patient Information Leaflet

Depo-Provera® 150 mg/ml Vial




Medroxyprogesterone Acetate
Please read all of this leaflet carefully before you start using this
method of contraception
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, nurse or
healthcare provider.
• This medicine has been prescribed for you. Do not pass it on to
others. It may harm them, even if their symptoms are the same
as yours.
• If any of the side effects get serious, or if you notice any side
effects not listed in this leaflet, please tell your doctor, nurse or
healthcare provider.
IMPORTANT INFORMATION YOU SHOULD KNOW ABOUT DEPOPROVERA
Depo-Provera is a very effective injectable contraceptive which
gives 12 weeks’ continuous contraception with each injection.
The effect is not reversible once the injection is given.
• You must have injections of this contraceptive regularly every 12
weeks, otherwise you may risk becoming pregnant (see Section 3
‘How to use Depo-Provera’).
• Depo-Provera may not be suitable for every woman. You will need
to discuss with your doctor or healthcare professional providing
your contraception whether it is suitable for you, especially if you
wish to use it for more than 2 years (See Section 1 ‘What DepoProvera is and what it is used for’).
• Depo-Provera may not be suitable for you if you have a history of
certain medical conditions (see Section 2 under ‘Before you use
Depo-Provera’) or if you are taking a medicine called
aminoglutethiamide that thins the blood (see Section 2 under
‘Taking other medicines’). Your doctor or nurse should take a full
medical history before prescribing Depo-Provera.
• Regular use of Depo-Provera causes a gradual loss of bone
mineral density (see Section 4 ‘Possible side effects’). For a small
number of patients that were followed-up, the average bone
mineral density returned to average 1-3 years after they stopped
using Depo-Provera. Teenagers who are rapidly developing their
bones may be at particular risk and should only use Depo-Provera
if other methods of contraception have been discussed and
considered unsuitable or unacceptable.
In this leaflet:
1. What Depo-Provera is and what it is used for
2. Before you use Depo-Provera
3. How to use Depo-Provera
4. Possible side effects
5. How to store Depo-Provera
6. Further information
1. What Depo-Provera is and what it is used for
Depo-Provera is a long acting contraceptive. The active ingredient in
Depo-Provera, medroxyprogesterone acetate (MPA), is similar to (but
not the same as) the natural hormone progesterone that is produced in
the ovaries during the second half of your menstrual cycle.
Depo-Provera acts by preventing an egg from fully developing and
being released from the ovaries during your menstrual cycle. If an egg
is not released it cannot become fertilised by sperm and result in
pregnancy. Depo-Provera also causes changes in the lining of your
womb that makes it less likely for pregnancy to occur. It also thickens
the mucus at the entrance of the womb, making it more difficult for
sperm to enter.
Depo-Provera can be used:
• For long-term contraception where you and the person who
provides your contraception (e.g. your doctor or healthcare
professional) have decided that this method is the most suitable for
you.
• If you wish to use Depo-Provera for more than 2 years your doctor
or healthcare professional may wish to re-evaluate the risks and
benefits of using Depo-Provera to make sure that it is still the best
option for you.
• In teenagers only after other methods of contraception have been
discussed with the healthcare professional who provides your
contraception and considered to be unsuitable or unacceptable.
• For just one or two occasions in the following cases:
• if your partner is undergoing a vasectomy, to give you
protection until the vasectomy becomes effective
• if you are being immunised against rubella, to prevent
pregnancy during the period of activity of the virus
• if you are awaiting sterilisation.
2. Before you use Depo-Provera
Do not use Depo-Provera:
• If you are allergic (hypersensitive) to the active ingredient (MPA) or
any of the other ingredients. There is a small risk of a severe
allergic reaction to Depo-Provera that will require emergency
medical treatment.
• If you think you may be pregnant.
• If you have had, or think you may have, hormone-dependent
cancer of the breast or reproductive organs.
• If you have unexplained vaginal bleeding.
• If you have liver disease.
• If you have never had a period.
• If you are using certain medicines such as high dose
glucocorticoids (steroids), anti-epileptics, and thyroid hormones.
Tell the person who provides your contraception if you are taking
these or any other medicines - they may recommend a more
suitable method of contraception.
Take special care with Depo-Provera:
Before your doctor or healthcare professional prescribes DepoProvera, you may need to have a physical examination. It is important
to tell your doctor or healthcare professional if you have, or have had
in the past, any of the following conditions. Your doctor will then
discuss with you whether Depo-Provera is suitable for you.
• Migraine headaches – if you develop migraine you should consult
your doctor before receiving further injections of Depo-Provera
• Diabetes or a family history of diabetes







Severe pain or swelling in the calf (indicating a possible clot in the
leg, which may be called phlebitis)
Blood clotting disorders such as deep vein thrombosis (blood clot
in the legs), pulmonary embolus (blood clot in the lung) or a stroke
you should not receive further injections of Depo-Provera
Problems with your eyesight while using Depo-Provera; for
example a sudden partial or complete loss of vision or double
vision
Past history of or current depression
Problems with your liver or liver disease
History of heart disease or cholesterol problems including any
family history
If you have recently had a ‘hydatidiform mole’ which is a type of
abnormal pregnancy.

Cervical smear testing:
The results of a cervical smear and some laboratory tests could also
be affected if you are using Depo-Provera so it is important that you
tell your doctor.
Protection against sexually transmitted diseases:
Depo-Provera does not protect against HIV infection (AIDS) and other
sexually transmitted diseases.
Taking other medicines:
• Tell your doctor or healthcare professional if you are taking a
medicine called aminoglutethiamide or other medicines that thin
your blood (anticoagulants) as these may affect the way DepoProvera works.
• Always tell your doctor or healthcare professional who treats you
that you are using Depo-Provera as a contraceptive if you are
taking or have recently taken any other medicines, even those you
bought yourself without a prescription, because medicines can
sometimes interact with each other.
Pregnancy:
• Because Depo-Provera is such an effective contraceptive method,
the risk of accidental pregnancy for women who have their
injections regularly (every 12 weeks) is very low.
• If you think you may have become pregnant while using DepoProvera for contraception, tell your doctor immediately.
Effect on future fertility:
• Your usual level of fertility will return when the effect of the
injection has worn off.
• This takes different amounts of time in different women, and does
not depend on how long you have been using Depo-Provera.
• In most women the effect will have worn off 5 to 6 months after the
last injection.
• Over 80% of women trying to get pregnant will conceive within a
year of the first missed injection.
• Some women have got pregnant in the first month after missing an
injection.
If you are breast-feeding:
• Depo-Provera does not prevent the breast from producing milk so
nursing mothers can use it, however, it is better for the baby that
for the first few weeks after birth its mother’s milk contains no
traces of any medicines, including Depo-Provera.
• Your doctor or healthcare professional may advise that you wait
until at least 6 weeks after your baby has been born before you
start using Depo-Provera for contraception.
• If a baby is exposed to Depo-Provera in the breast milk, no harmful
effects have been seen in babies and children.
Driving and using machines:
Depo-Provera may cause headaches and dizziness. Therefore be
careful until you know whether this medicine affects your ability to drive
or use machines. If you have any concerns discuss them with your
doctor.
Important information about some of the ingredients of DepoProvera:
The active ingredient in Depo-Provera is medroxyprogesterone acetate
(MPA). Depo-Provera also contains methyl parahydroxybenzoate,
macrogol, polysorbate 80, propyl parahydroxybenzoate, sodium
chloride and water
Hydrochloric acid or sodium hydroxide may also be added when the
product is being made to adjust the acidity or alkalinity of the product
to the correct level.
3. How to use Depo-Provera
This medicine will be given to you by your doctor or healthcare
professional.
Depo-Provera is given every 12 weeks as a single intramuscular
injection of 1 ml (150 mg medroxyprogesterone acetate) into the
buttock or upper arm. The injection is given during the first 5 days after
the beginning of a normal menstrual period.
Following childbirth the first Depo-Provera injection can be given within
5 days after childbirth if you are not breast-feeding.
Provided that the injection is given at the times stated above, then you
are protected from pregnancy straight away and there is no need to
take extra precautions.
Depo-Provera works as a contraceptive for 12 weeks in your body.
There is no way of reversing the injection once it is given.
For effective contraceptive cover Depo-Provera MUST be given every
12 weeks. Make sure that you or your doctor makes your next
appointment for 12 weeks time.
If you miss an injection of Depo-Provera:
If you miss your injection or are late getting your next injection (ie wait
longer than 12 weeks between injections), there is a greater risk that
you could become pregnant. Ask your doctor or healthcare
professional to find out when you should receive your next injection of
Depo-Provera and which type of contraception should be used in the
meantime.

Switching from other methods of contraception:
When you switch from other contraceptive methods, your doctor will
make sure you are not at risk of becoming pregnant by giving you your
first injection at the appropriate time. If you switch from oral
contraceptives, you should have your first injection of Depo-Provera
within 7 days after taking your last pill.
If you have any further questions on the use of this product ask your
doctor or healthcare professional.
4. Possible side effects
Like all medicines Depo-Provera can cause side effects although not
everybody gets them.
There is a low risk of anaphylactic responses (serious allergic
reactions which may need urgent medical attention or hospitalization).
Possible symptoms include: swelling of the face, lips, tongue or throat,
or difficulty breathing or swallowing, skin rashes, shock or collapse.
Deep vein thrombosis (DVT) is a condition in which a blood clot forms
in one of your deep veins, usually in your leg. Signs of possible DVT
include: swelling of the affected leg, pain and tenderness in the
affected leg (you may also find it difficult to stand properly with your full
weight on the affected leg), a change in the colour of your skin, for
example, redness or skin that feels warm or hot to the touch.
Women who use Depo-Provera tend to have lower bone mineral
density than women of the same age who have never used it. The
effects of Depo-Provera are greatest in the first 2-3 years of use.
Following this, bone mineral density tends to stabilise and there
appears to be some recovery when Depo-Provera is stopped. It is not
yet possible to say whether Depo-Provera increases the risk of
osteoporosis (weak bones) and fractures in later life.
Tell your doctor immediately if you experience any of the above
symptoms.
Common side effects (occur in more than 10 out of every 1,000
patients)
These include:
abdominal pain or discomfort, bloating, feeling sick, vaginal discharge
or inflammation, changes in appetite, backpain, headaches, dizziness,
irregular periods, very light or no periods (amenorrhoea), breast pain
or tenderness, pelvic pain, hot flushes, acne, hair loss, rash, weakness
or tiredness, injection site reactions, feeling of weakness, tingling or
numbness in the hands and feet, depression, nervousness, insomnia
(difficulty sleeping), irritability, anorgasmia (failure to climax during
sexual intercourse), emotional disturbance, intermenstrual bleeding
(bleeding between periods), menorrhagia (heavy periods).
Uncommon side effects (occurs in fewer than 10 out of every 1,000
patients)
These include:
jaundice (this will cause yellowing of the skin and the whites of the
eyes), hypertension, varicose veins, thrombophlebitis (inflammation of
part of a vein), pulmonary embolism (blood clot in the lungs which
causes chest pain and breathlessness), allergic reactions (such as
swelling on the face and throat), abnormal liver enzymes (blood tests
used to measure liver function), feeling of dizziness or ‘spinning’,
abdominal discomfort, change in weight, fluid retention, joint pain,
muscle cramps, pain in legs and arms, somnolence (sleepiness),
migraine, convulsion (‘fit’), vaginal dryness, painful periods, change in
breast size, painful intercourse, ovarian cyst, premenstrual syndrome,
infections of the urinary tract or reproductive organs, an increase in
thickness of the lining of the womb, dark patches on the skin, bruising,
excessive hair growth, itching, skin rash, swelling, chest pain, fever,
abnormal cervical smear results, anxiety, difficulty breathing.
Rare side effects (occurs in less than 1 out of every 1,000 patients)
These include: tachycardia (faster heart beat), breast lumps or nipple
bleeding, thirst, hoarseness, rectal bleeding (bleeding from the anus),
paralysis, decreased glucose tolerance (abnormal blood sugar levels),
breast cancer, anaemia (reduction in red blood cells which can make
the skin pale and cause weakness or breathlessness).
Other side effects that have been observed include:
Blood clotting disorders, deep vein thrombosis (blood clots forming in
the veins, usually the legs), disturbed liver function. osteoporosis
(thinning of the bones) including fractures, loss of bone mineral density
(a test to measure the strength of bones), swelling of ankles or wrists,
abnormal uterine bleeding (irregular, increase, decrease), milky
discharge from breasts in women who are not breastfeeding, vaginal
cysts, milk supply stopping (in breastfeeding mothers), feeling
pregnant, delay in becoming pregnant after stopping Depo-Provera,
scaling of skin, scleroderma (a rare autoimmune disease that affects
the skin and other parts of the body),weakness in the face muscles,
fainting, blood disorder, skin striae (stretch marks).
If any of the side effects get serious, or if you notice any side effects
not listed in this leaflet, please tell your doctor or healthcare
professional.
Possible effect on your periods:
Depo-Provera will usually disturb the pattern of a woman’s period.
After the first injection it is most likely that you will have irregular,
possibly lengthy bleeding or spotting. This will continue in some
women. This is quite normal and nothing to worry about.
One third of women will not have any bleeding at all after the first
injection. After 4 injections, most women find that their periods have
stopped completely. Not having periods is nothing to worry about.
If you experience very heavy or prolonged bleeding you should talk to
your doctor. This happens rarely but can be treated.
When you stop taking Depo-Provera your periods will return to normal
in a few months.
Possible effects on your bones:
Depo-Provera works by lowering levels of estrogen and other
hormones. However, low estrogen levels can cause bones to become
thinner (by reducing bone mineral density). Women who use DepoProvera tend to have lower bone mineral density than women of the
same age who have never used it. The effects of Depo-Provera are
greatest in the first 2-3 years of use. Following this, bone mineral
density tends to stabilise and there appears to be some recovery when
Depo-Provera is stopped. It is not yet possible to say whether DepoProvera increases the risk of osteoporosis (weak bones) and fractures
in later life.

The following are risk factors in the development of osteoporosis in
later life. You should discuss with your doctor before starting treatment
if you have any of the following as an alternative contraceptive may be
more suitable to your needs;
• Chronic alcohol and/or tobacco use
• Chronic use of drugs that can reduce bone mass, e.g. epilepsy
medication or steroids
• ·Low body mass index or eating disorder, e.g. anorexia nervosa or
bulimia
• Previous low trauma fracture that was not caused by a fall
• Strong family history of osteoporosis
Teenagers (up to 18 years): Normally, the bones of teenagers are
rapidly growing and increasing in strength. The stronger the bones are
when adulthood is reached, the greater the protection against
osteoporosis in later life. Since Depo-Provera may cause teenage
bones to become thinner at a time when they should be growing, its
effect may be particularly important in this age group. Bones start to
recover when Depo-Provera is stopped, but it is not yet known whether
the bone mineral density reaches the same levels as it would have if
Depo-Provera had never been used. You should therefore discuss
whether another form of contraception might be more suitable for
you with the person who provides your contraception before
starting Depo-Provera.
If you use Depo-Provera, it may help your bones if you take regular
weight-bearing exercise and have a healthy diet, including an
adequate intake of calcium (e.g. in dairy products) and vitamin D
(e.g. in oily fish).
Possible risk of cancer: Studies of women who have used different
forms of contraception found that women who used Depo-Provera for
contraception had no increase in overall risk of developing cancer of
the ovary, womb, cervix or liver.
Possible risk of breast cancer
Breast cancer is rare among women under 40 years of age whether or
not they use hormonal contraceptives. Depo-Provera may increase the
risk of breast cancer slightly compared with women who have never
used it. However, any excess risk is small in relation to the overall risk
of breast cancer, particularly in young women.
Older women have a higher baseline risk of breast cancer and
therefore the increase in the number of cases due to Depo-Provera is
greater in older women than in younger women.
In absolute terms this means that:
A 15 year old who uses Depo-Provera for 5 years increases her
chance of developing breast cancer by a negligible amount by the age
of 30.
A 25 year old who uses Depo-Provera for 5 years increases her
chance of developing breast cancer by the age of 40 from 44 cases
per 10,000 women (without Depo-Provera use) to up to 47 cases per
10,000 women i.e. an extra 3 cases/10,000.
A 35 year old who uses Depo-Provera for 5 years increases her
chance of developing breast cancer by the age of 50 from 160 cases
per 10,000 women (without Depo-Provera use) to 170 cases per
10,000 women i.e. an extra 10 cases/10,000.
Possible risk of forming an abscess at the injection site:
As with any intramuscular injection, there is a risk of an abscess
forming at the site of injection. This may require medical or surgical
attention.
Possible risk of weight gain:
Some women gained weight while using Depo-Provera. Studies show
that over the first 1-2 years of use, the average weight gain was
5-8 lbs. Women completing 4-6 years of therapy gained an average of
14-16.5 lbs.
5. How to store Depo-Provera
Keep out of reach and sight of children.
Do not refrigerate or freeze.
Do not use Depo-Provera after the last day of the month shown in the
expiry date stated on the vial and the carton.
6. Further Information
What Depo-Provera contains:
The active ingredient in Depo-Provera is medroxyprogesterone acetate
(MPA). Each dose (1 millilitre) of Depo-Provera contains 150 mg of
medroxyprogesterone acetate. Depo-Provera also contains methyl
parahydroxybenzoate, macrogol, polysorbate 80, propyl
parahydroxybenzoate, sodium chloride and water. Hydrochloric acid or
sodium hydroxide may also be added when the product is being made
to adjust the acidity or alkalinity of the product to the correct level.
What Depo-Provera looks like and contents of the pack:
Depo-Provera is a white sterile suspension. Each vial contains 1
millilitre (ml) of Depo-Provera. Depo-Provera is supplied in cartons
containing one vial.
Manufacturer:
Pfizer Manufacturing Belgium NV/SA, Rijksweg 12, B-2870 Puurs
Belgium.
Procured from within the E.U, and repackaged by product licence
holder: Munro Wholesale Medical Supplies Ltd., 3 Young Place,
East Kilbride, G75 0TD.
PL: 03243/0693 Depo-Provera® 150 mg/ml
This leaflet was revised: 09.09.2011 0693/5-P
® is a registered trademark of Pharmacia Ltd
POM

Information for Doctors and Pharmacists

Depo-Provera® 150 mg/ml Vial
Medroxyprogesterone Acetate
For further information consult the Summary of Product Characteristics.
Description
Depo-Provera is a white, sterile suspension for injection. Each 1 ml vial
contains 150 mg medroxyprogesterone acetate Ph. Eur. Excipients are
methyl parahydroxybenzoate, macrogol, polysorbate 80, propyl
parahydroxybenzoate, sodium chloride, water for injection. Hydrochloric
acid or sodium hydroxide may be present as pH adjusters.
Uses
Depo-Provera is a long-term contraceptive agent suitable for use in women
who have been appropriately counselled concerning the likelihood of
menstrual disturbance and the potential for a delay in return to full fertility.
Depo-Provera may also be used for short-term contraception in the
following circumstances:
• For partners of men undergoing vasectomy, for protection until the
vasectomy becomes effective.
• In women who are being immunised against rubella, to prevent
pregnancy during the period of activity of the virus.
• In women awaiting sterilisation.
Since loss of bone mineral density (BMD) may occur in females of all ages
who use Depo-Provera injection long-term, a risk/benefit assessment,
which also takes into consideration the decrease in BMD that occurs
during pregnancy and/or lactation, should be considered. It is of the
greatest importance that adequate explanations of the long-term nature of
the product, of its possible side-effects and of the impossibility of
immediately reversing the effects of each injection are given to potential
users and that every effort is made to ensure that each patient receives
such counselling as to enable her to fully understand these explanations.
Patient information leaflets are supplied by the manufacturer. It is
recommended that the doctor uses these leaflets to aid counselling of the
patient before giving the injection of Depo-Provera.
Dosage
Each ml of suspension contains 150 mg medroxyprogesterone acetate Ph.
Eur. The sterile aqueous suspension of Depo-Provera should be
vigorously shaken just before use to ensure that the dose being given
represents a uniform suspension of Depo-Provera. Doses should be given
by deep intramuscular injection into the buttock or arm.
Care should be taken to ensure that the depot injection is given into the
muscle tissue, preferably the gluteus maximus, both other muscle tissue
such as the deltoid may be used and the site of injection should be
cleansed using standard methods prior to administration of the injection.
Assembly of syringe for single use:
1. Remove tip cap.
2. Position needle using aseptic technique.
3. Remove needle shield. The syringe is now ready for use.
Administration
First injection: To provide contraceptive cover in the first cycle of use, an
injection of 150 mg i.m. should be given during the first five days of a
normal menstrual cycle. If the injection is carried out according to these
instructions, no additional contraceptive cover is required.
Postpartum: To increase assurance that the patient is not pregnant at the
time of first administration, this injection should be given within 5 days
postpartum if not breast-feeding.
There is evidence that women prescribed Depo-Provera in the immediate
puerperium can experience prolonged and heavy bleeding. Because of
this, the drug should be used with caution in the puerperium. Women who
are considering use of the product immediately following delivery or
termination should be advised that the risk of heavy or prolonged bleeding
may be increased.
Doctors are reminded that in the non breast-feeding postpartum patient,
ovulation may occur as early as week 4. If the puerperal woman will be
breast-feeding, the initial injection should be given no sooner than six
weeks postpartum, when the infant’s enzyme system is more fully
developed. Further injections should be given at 12 week intervals.
Further doses: These should be given at 12 week intervals, however, as
long as the injection is given no later than five days after this time, no
additional contraceptive measures (e.g. barrier) are required.
(NB For partners of men undergoing vasectomy a second injection of 150
mg i.m. 12 weeks after the first may be necessary in a small proportion of
patients where the partner’s sperm count has not fallen to zero.) If the
interval from the preceding injection is greater than 89 days (12 weeks and
five days) for any reason, then pregnancy should be excluded before the
next injection is given and the patient should use additional contraceptive
measures (e.g. barrier) for fourteen days after this subsequent injection.
Children: Depo-Provera is not indicated before menarche. Data in
adolescent females (12-18 years) is available. Other than concerns about
loss of BMD, the safety and effectiveness of Depo-Provera is expected to
be the same for adolescents after menarche and adult females.
Switching from other Methods of Contraception: Depo-Provera should be
given in a manner that ensures continuous contraceptive coverage. This
should be based upon the mechanism of action of other methods (e.g.
patients switching from oral contraceptives should have their first injection
of Depo-Provera within 7 days of taking their last active pill).
Hepatic Insufficiency: The effect of hepatic disease on the
pharmacokinetics of Depo-Provera is unknown. As Depo-Provera largely
undergoes hepatic elimination it may be poorly metabolised in patients with
severe liver insufficiency (see Contraindications).
Renal Insufficiency: The effect of renal disease on the pharmacokinetics of
Depo-Provera is unknown. No dosage adjustment should be necessary in
women with renal insufficiency, since Depo-Provera is almost exclusively
eliminated by hepatic metabolism.
Contra-indications
Depo-Provera is contra-indicated in patients with a known sensitivity to
medroxyprogesterone acetate or any ingredient of the vehicle.
Depo-Provera should not be used during pregnancy, either for diagnosis or
therapy.
Depo-Provera is contra-indicated as a contraceptive at the above dosage
in known or suspected hormone-dependent malignancy of breast or genital
organs.
Whether administered alone or in combination with oestrogen, DepoProvera should not be employed in patients with abnormal uterine bleeding
until a definite diagnosis has been established and the possibility of genital
tract malignancy eliminated.
Special warnings and precautions for use
Warnings:
Loss of Bone Mineral Density:
Use of Depo-Provera reduces serum estrogen levels and is associated
with significant loss of BMD due to the known effect of estrogen deficiency
on the bone remodelling system. Bone loss is greater with increasing
duration of use, however BMD appears to increase after Depo-Provera is
discontinued and ovarian estrogen production increases.
This loss of BMD is of particular concern during adolescence and early
adulthood, a critical period of bone accretion. It is unknown if use of DepoProvera by younger women will reduce peak bone mass and increase the
risk for fracture in later life.

A study to assess the BMD effects of medroxyprogesterone acetate IM
(Depo-Provera, DMPA) in adolescent females showed that its use was
associated with a significant decline in BMD from baseline. In the small
number of women who were followed-up, mean BMD recovered to around
baseline values by 1- 3 years after discontinuing treatment. In adolescents,
Depo-Provera may be used, but only after other methods of contraception
have been discussed with the patients and considered to be unsuitable or
unacceptable.
In women of all ages, careful re-evaluation of the risks and benefits of
treatment should be carried out in those who wish to continue use for more
than 2 years. In particular, in women with significant lifestyle and/or
medical risk factors for osteoporosis, other methods of contraception
should be considered prior to use of Depo-Provera.
Significant risk factors for osteoporosis include:
• Alcohol abuse and/or tobacco use
• Chronic use of drugs that can reduce bone mass, e.g., anticonvulsants
or corticosteroids
• Low body mass index or eating disorder, e.g., anorexia nervosa or
bulimia
• Previous low trauma fracture
• Family history of osteoporosis
A retrospective cohort study using data from the General Practice
Research Database (GPRD) reported that women using MPA injections
(DMPA), have a higher risk of fracture compared with contraceptive users
with no recorded use of DMPA (incident rate ratio 1.41, 95% CI 1.35-1.47
for the five year follow-up period); it is not known if this is due to DMPA, or
to other related lifestyle factors which have a bearing on fracture rate. By
contrast, in women using DMPA, the fracture risk before and after starting
DMPA was not increased (relative risk 1.08, 95% CI 0.92-1.26).
Importantly, this study could not determine whether use of DMPA has an
effect on fracture rate later in life.
For further information on BMD changes in both adult and adolescent
females, as reported in recent clinical studies, refer to section 5.1 of the
SPC. Adequate intake of calcium and Vitamin D, whether from the diet or
from supplements, is important for bone health in women of all ages.
Menstrual Irregularity: The administration of Depo-Provera usually causes
disruption of the normal menstrual cycle. Bleeding patterns include
amenorrhoea (present in up to 30% of women during the first 3 months
and increasing to 55% by month 12 and 68% by month 24); irregular
bleeding and spotting; prolonged (>10 days) episodes of bleeding (up to
33% of women in the first 3 months of use decreasing to 12% by month
12). Rarely, heavy prolonged bleeding may occur. Evidence suggests that
prolonged or heavy bleeding requiring treatment may occur in 0.5-4
occasions per 100 women years of use. If abnormal bleeding persists or is
severe, appropriate investigation should take place to rule out the
possibility of organic pathology and appropriate treatment should be
instituted when necessary. Excessive or prolonged bleeding can be
controlled by the coadministration of oestrogen. This may be delivered
either in the form of a low dose (30 micrograms oestrogen) combined oral
contraceptive pill or in the form of oestrogen replacement therapy such as
conjugated equine oestrogen (0.625-1.25 mg daily). Oestrogen therapy
may need to be repeated for 1-2 cycles. Long-term co-administration of
oestrogen is not recommended.
Return to Fertility: There is no evidence that Depo-Provera causes
permanent infertility. Pregnancies have occurred as early as 14 weeks
after a preceding injection, however, in clinical trials, the mean time to
return of ovulation was 5.3 months following the preceding injection.
Women should be counselled that there is a potential for delay in return to
full fertility following use of the method, regardless of the duration of use,
however, 83% of women may be expected to conceive within 12 months of
the first "missed" injection (i.e. 15 months after the last injection
administered). The median time to conception was 10 months (range 4-31)
after the last injection.
Cancer Risks: Long-term case-controlled surveillance of Depo-Provera
users found no overall increased risk of ovarian, liver, or cervical cancer
and a prolonged, protective effect of reducing the risk of endometrial
cancer in the population of users.
Breast cancer is rare among women under 40 years of age whether or not
they use hormonal contraceptives.
Results from some epidemiological studies suggest a small difference in
risk of the disease in current and recent users compared with never-users.
Any excess risk in current and recent DMPA users is small in relation to
the overall risk of breast cancer, particularly in young women (see below),
and is not apparent after 10 years since last use. Duration of use does not
seem to be important.
Possible number of additional cases of breast cancer diagnosed up to 10
years after stopping injectable progestogens*
Age at last use of
DMPA

No of cases per
10,000 women who
are never users
20
Less than 1
30
44
40
160
*based on use for 5 years

Possible additional
cases per 10,000 DMPA
users
Much less than 1
2-3
10

Weight Gain: There is a tendency for women to gain weight while on DepoProvera therapy. Studies indicate that over the first 1-2 years of use,
average weight gain was 5-8 lbs. Women completing 4-6 years of therapy
gained an average of 14-16.5 lbs. There is evidence that weight is gained
as a result of increased fat and is not secondary to an anabolic effect or
fluid retention.
Anaphylaxis: Reports of anaphylactic responses (anaphylactic reactions,
anaphylactic shock, anaphylactoid reactions) have been received.
Thromboembolic Disorders: Should the patient experience pulmonary
embolism, cerebrovascular disease or retinal thrombosis while receiving
Depo-Provera, the drug should not be readministered.
Psychiatric Disorders: Patients with a history of endogenous depression
should be carefully monitored. Some patients may complain of
premenstrual-type depression while on Depo-Provera therapy.
Abscess formation: As with any intramuscular injection, especially if not
administered correctly, there is a risk of abscess formation at the site of
injection, which may require medical and/or surgical intervention.
Precautions:
History or emergence of the following conditions requires careful
consideration and appropriate investigation: migraine or unusually severe
headaches, acute visual disturbances of any kind, pathological changes in
liver function and hormone levels. Patients with thromboembolic or
coronary vascular disease should be carefully evaluated before using
Depo-Provera.
A decrease in glucose tolerance has been observed in some patients
treated with progestogens. The mechanism for this decrease is obscure.
For this reason, diabetic patients should be carefully monitored while
receiving progestogen therapy.
Rare cases of thromboembolism have been reported with use of DepoProvera, but causality has not been established.

The effects of medroxyprogesterone acetate on lipid metabolism have
been studied with no clear impact demonstrated. Both increases and
decreases in total cholesterol, triglycerides and low-density lipoprotein
(LDL) cholesterol have been observed in studies. The use of DepoProvera appears to be associated with a 15-20 % reduction in serum high
density lipoprotein (HDL) cholesterol levels which may protect women from
cardiovascular disease. The clinical consequences of this observation are
unknown.
The potential for an increased risk of coronary disease should be
considered prior to use.
Doctors should carefully consider the use of Depo-Provera in patients with
recent trophoblastic disease before levels of human chorionic
gonadotrophin have returned to normal.
Physicians should be aware that pathologists should be informed of the
patient’s use of Depo-Provera if endometrial or endocervical tissue is
submitted for examination.
The results of certain laboratory tests may be affected by the use of DepoProvera. These include gonadotrophin levels (decreased), plasma
progesterone levels (decreased), urinary pregnanediol levels (decreased),
plasma oestrogen levels (decreased), plasma cortisol levels (decreased),
glucose tolerance test, metyrapone test, liver function tests (may increase),
thyroid function tests (protein bound iodine levels may increase and T3
uptake levels may decrease). Coagulation test values for prothrombin
(Factor II), and Factors VII, VIII, IX and X may increase.

Pharmacodynamic Properties
Medroxyprogesterone acetate exerts anti-oestrogenic, anti-androgenic and
antigonadotrophic effects.
BMD Changes in Adult Women: A study comparing changes in BMD in
women using Depo-Provera with women using medroxyprogesterone
acetate injection (150 mg IM) showed no significant differences in BMD
loss between the two groups after two years of treatment. Mean percent
changes in BMD in the Depo-Provera group are listed in Table 1
Table 1. Mean Percent Change from Baseline in BMD in Women Using
DEPO-PROVERA by Skeletal Site

Lumbar Spine

Total Hip

Femoral Neck

Time on
treatment

N

N

N

1 year

166

2 year

106

Mean %
Change
(95% CI)
-2.7
(-3.1 to
-2.3)
-4.1
(-4.6 to
-3.5)

166

106

Mean %
Change
(95% CI)
-1.7
(-2.1 to
-1.3)
-3.5
(-4.2 to
-2.7)

166

106

Mean %
Change
(95% CI)
-1.9 (-2.5
to -1.4)
-3.5
(-4.3 to
-2.6)

Interaction with Other Medicaments and Other Forms of Interaction
Aminoglutethimide administered concurrently with Depo-Provera may
significantly depress the bioavailability of Depo-Provera.
Interactions with other medicinal treatments (including oral anticoagulants)
have rarely been reported, but causality has not been determined. The
possibility of interaction should be borne in mind in patients receiving
concurrent treatment with other drugs.
The clearance of medroxyprogesterone acetate is approximately equal to
the rate of hepatic blood flow. Because of this fact, it is unlikely that drugs
which induce hepatic enzymes will significantly affect the kinetics of
medroxyprogesterone acetate. Therefore, no dose adjustment is
recommended in patients receiving drugs known to affect hepatic
metabolising enzymes.

In another controlled, clinical study adult women using
medroxyprogesterone acetate injection (150 mg IM) for up to 5 years
showed spine and hip mean BMD decreases of 5-6%, compared to no
significant change in BMD in the control group. The decline in BMD was
more pronounced during the first two years of use, with smaller declines in
subsequent years. Mean changes in lumbar spine BMD of –2.86%,
-4.11%, -4.89%, -4.93% and –5.38% after 1, 2, 3, 4 and 5 years,
respectively, were observed. Mean decreases in BMD of the total hip and
femoral neck were similar. Please refer to Table 2 below for further details.
After stopping use of medroxyprogesterone acetate injection (150 mg IM),
BMD increased towards baseline values during the post-therapy period. A
longer duration of treatment was associated with a slower rate of BMD
recovery.

Pregnancy and Lactation
Doctors should check that patients are not pregnant before the initial
injection of Depo-Provera, and also if administration of any subsequent
injection is delayed beyond 89 days (12 weeks and five days).
Infants from accidental pregnancies that occur 1-2 months after injection of
Depo-Provera may be at an increased risk of low birth weight, which in turn
is associated with an increased risk of neonatal death. The attributable risk
is low because such pregnancies are uncommon.
Children exposed to medroxyprogesterone acetate in utero and followed to
adolescence, showed no evidence of any adverse effects on their health
including their physical, intellectual, sexual or social development.
Medroxyprogesterone acetate and/or its metabolites are secreted in breast
milk, but there is no evidence to suggest that this presents any hazard to
the child. Infants exposed to medroxyprogesterone via breast milk have
been studied for developmental and behavioural effects to puberty. No
adverse effects have been noted.

Table 2. Mean Percent Change from Baseline in BMD in Adults by Skeletal
Site and Cohort after 5 Years of Therapy with Medroxyprogesterone
acetate 150 mg IM and after 2 Years Post-Therapy or 7 Years of
Observation (Control)

Undesirable effects
In a large clinical trial of over 3900 women, who were treated with DepoProvera for up to 7 years, the following adverse events were reported.
The following adverse events were commonly (by more than 5% of
subjects) reported: menstrual irregularities (bleeding and/or amenorrhoea),
weight changes, headache, nervousness, abdominal pain or discomfort,
dizziness, asthenia (weakness or fatigue).
Adverse events reported by 1% to 5% of subjects using Depo-Provera
were: decreased libido or anorgasmia, backache, leg cramps, depression,
nausea, insomnia, leucorrhoea, acne, vaginitis, pelvic pain, breast pain, no
hair growth or alopecia, bloating, rash, oedema, hot flushes.
Adverse reactions are listed according to the following categories:
Very Common >10%, Common ≥1% and < 10%, Uncommon >0.1% and
<1%, Rare < 0.1%, Unknown (cannot be estimated from the available
data)
Ear and Labyrinth Disorders: Uncommon: Vertigo.
Gastrointestinal Disorders: Very common: Abdominal pain or discomfort.
Common: Bloating, nausea. Uncommon: Abdominal distension,
gastrointestinal disturbances. Rare: Rectal bleeding.
Infection & Infestations: Common: Vaginitis.
Metabolism & Nutrition Disorders: Common: Appetite decrease, appetite
increase Uncommon: weight increase, weight decrease, fluid retention.
Musculoskeletal, Connective Tissue & Bone Disorders: Common:
backpain. Uncommon: Arthralgia, muscle cramps, pain in limbs. Frequency
not known: Osteoporosis including osteoporotic fractures, loss of bone
mineral density, axillary swelling.
Nervous System Disorders: Very common: Headaches. Common:
Dizziness. Uncommon: Somnolence, migraine, convulsions. Unknown:
Syncope.
Reproductive System & Breast Disorders: Common: Amenorrhea, breast
pain/tenderness, intermenstrual bleeding, menometrorrhagia,
menorrhagia, pelvic pain, leucorrhoea. Uncommon: Vaginal discharge,
vulvovaginal dryness, dysmenorrhea, change in breast size, dyspareunia,
ovarian cyst, premenstrual syndrome, genitourinary infection, uterine
hyperplasia. Rare: Breast lumps or nipple bleeding. Frequency not known:
Abnormal uterine bleeding (irregular, increase, decrease), galactorrhea,
vaginal cysts, prevention of lactation, sensation of pregnancy, lack of
return to fertility.
Vascular Disorders: Common: Hot flushes. Uncommon: Hypertension,
varicose veins, thrombophlebitis, pulmonary embolism. Frequency not
known: Thromboembolic disorders, deep vein thrombosis.
Cardiovascular Disorders: Rare: Tachycardia.
Immune System Disorders: Uncommon: Hypersensitivity reactions (e.g.
anaphylaxis & anaphylactoid reactions, angioedema).
Hepato-biliary disorders: Uncommon: Abnormal liver enzymes, jaundice.
Frequency not known: Disturbed liver function.
Skin & Subcutaneous Tissue Disorders: Common: Acne, alopecia,
rash.Uncommon: Chloasma, dermatitis, ecchymosis, hirsutism, pruritus,
melasma, urticaria, oedema. Frequency not known: skin striae,
scleroderma.
General Disorders and Administration Site Conditions: Common: Fatigue,
injection site reactions (such as pain or abscess), asthenia, paraesthesia.
Uncommon: Chest pain, pyrexia.Rare: Thirst, hoarseness, paralysis.
Frequency not known: Facial palsy.
Investigations: Uncommon: Cervical smear abnormal. Rare: Decreased
glucose tolerance.
Psychiatric Disorders: Common: Anorgasmia, depression, nervousness,
emotional disturbance, libido decreased, mood disorder, irritability,
insomnia. Uncommon: Anxiety.
Neoplasms Benign, Malignant and Unspecified (Incl. Cysts and Polyps):
Rare: Breast cancer.
Blood and lymphatic system disorders: Rare: Anaemia. Frequency
unknown: Blood dyscrasia.
Respiratory, thoracic, and mediastinal disorders: Uncommon: Dyspnoea.
Overdose No positive action is required other than cessation of therapy.

Time in
study

Spine

Total Hip

Femoral Neck

Medroxypro Control
gesterone
acetate

Medroxypro Control
gesterone
acetate

Medroxypro Control
gesterone
acetate

5 yrs*

n=33
-5.38%

n=105
0.43%

n=21
-5.16%

n=65
0.19%

n=34
-6.12%

n=106
-0.27%

7 yrs**

n=12
-3.13%

n=60
0.53%

n=7
-1.34%

n=39
0.94%

n=13
-5.38%

n=63
-0.11%

*The treatment group consisted of women who received
medroxyprogesterone acetate injection (150 mg IM) for 5 years and the
control group consisted of women who did not use hormonal contraception
for this time period.
** The treatment group consisted of women who received
medroxyprogesterone acetate Injection (150 mg IM) for 5 years and were
then followed up for 2 years post-use and the control group consisted of
women who did not use hormonal contraceptive for 7 years.
BMD Changes in Adolescent Females (12-18 years)
Results from an open-label, non-randomised, clinical study of
medroxyprogesterone acetate Injection (150 mg IM every 12 weeks for up
to 240 weeks (4.6 years), followed by post–treatment measurements) in
adolescent females (12-18 years) also showed that medroxyprogesterone
acetate IM use was associated with a significant decline in BMD from
baseline. Among subjects who received ≥ 4 injections/60-week period, the
mean decrease in lumbar spine BMD was - 2.1 % after 240 weeks (4.6
years); mean decreases for the total hip and femoral neck were -6.4 % and
-5.4 %, respectively. Post-treatment follow-up showed that, based on
mean values, lumbar spine BMD recovered to baseline levels
approximately 1 year after treatment was discontinued and that hip BMD
recovered to baseline levels approximately 3 years after treatment was
discontinued. However, it is important to note that a large number of
subjects discontinued from the study, therefore these results are based on
a small number of subjects (n=71 at 60 weeks and n=25 at 240 weeks
after treatment discontinuation). In contrast, a non-comparable cohort of
unmatched, untreated subjects, with different baseline bone parameters
from the DMPA users, showed mean BMD increases at 240 weeks of
6.4%, 1.7% and 1.9% for lumbar spine, total hip and femoral neck,
respectively.
Pharmacokinetic properties
Parenteral medroxyprogesterone acetate (MPA) is a long acting
progestational steroid. The long duration of action results from its slow
absorption from the injection site. Immediately after injection of 150 mg/ml
MPA, plasma levels were 1.7 ± 0.3 nmol/l. Two weeks later, levels were
6.8 ± 0.8 nmol/l. Concentrations fell to the initial levels by the end of 12
weeks. At lower doses, plasma levels of MPA appear directly related to the
dose administered. Serum accumulation over time was not demonstrated.
MPA is eliminated via faecal and urinary excretion. Plasma half-life is
about six weeks after a single intramuscular injection. At least 11
metabolites have been reported. All are excreted in the urine, some, but
not all, conjugated.
Shelf-life
The shelf-life is printed on labels and cartons. Do not use Depo-Provera
after this date.
Storage of the product
Store below 25°C and protect from freezing. Do not mix with other agents.
Discard any remaining contents after use.
Manufacturer :
Pfizer Manufacturing Belgium NV/SA, Rijksweg 12, B-2870 Puurs,
Belgium.
Procured from within the E.U, and repackaged by product licence holder:
Munro Wholesale Medical Supplies Ltd., 3 Young Place,
East Kilbride, G75 0TD.
PL: 03243/0693 Depo-Provera® 150 mg/ml
This leaflet was revised: 09.09.2011 0693/5-D
® is a registered trademark of Pharmacia Ltd

POM

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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